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Synthesis of controlled-size silver nanoparticles for the administration of methotrexate drug and its activity in colon and lung cancer cells

机译：用于甲氨蝶呤药物施用控制尺寸银纳米粒子的合成及其在结肠癌细胞中的活性

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A controlled synthesis of methotrexate (MTX) silver nanoparticles (AgNPs-MTX) using borohydride and citrate as reduction and reduction/capping agents, respectively, was performed in order to obtain AgNPs-MTX conjugates with a narrow size distribution. Their characterization showed polydispersed spherical shape nanoparticles with a mean size around 13 nm and distribution range between 7-21 nm. The presence of MTX was confirmed by FTIR and EDX analysis. Spectroscopic determinations suggest the chemisorption of MTX through a carboxylic group (-COOH) onto AgNPs via the exchange with a citrate molecule. Drug loading capacities calculated for AgNPs synthesized using different amounts of MTX were 28, 31 and 40%. In vitro drug release tests depicted similar release profiles for all conjugated amounts releasing between 77 to 85% of the initial MTX loaded into the AgNPs. With respect to free MTX, the addition of the nanocarrier delayed its release and also changed its pharmacokinetics. Free MTX is released after 3 hours following a first order kinetic model, whereas in the presence of AgNPs, a fast initial release is observed during the first 5 hours, followed by a plateau after 24 hours. In this case, AgNPs-MTX fitted a Higuchi model, where its solubilization is controlled by a diffusion process. Results obtained from flow cytometry of different cell lines treated with AgNPs-MTX demonstrated the combined anticancer effect of both reagents, decreasing the percentage of living cells in a colon cancer cell line (HTC-116) down to 40% after 48 hours of exposure. This effect was weaker but still significant for a lung cancer cell line (A-549). Finally, a zebrafish assay with AgNPs-MTX did not show any significant cytotoxic effect, confirming thereby the reduction of systemic drug toxicity achieved by coupling MTX to AgNPs. This observed toxicity reduction in the zebrafish model implies also a probable improvement of the usage of AgNPs-MTX in chemotherapy against human cancers.
机译：通过分别使用硼氢化硼和柠檬酸盐的对甲氨蝶呤（MTX）银纳米颗粒（AgNPS-MTX）的控制合成分别为还原和还原/封端剂，以获得具有窄尺寸分布的AgNPS-MTX缀合物。它们的表征显示了多分散的球形纳米颗粒，其平均尺寸约为13nm，分布范围为7-21nm。通过FTIR和EDX分析证实了MTX的存在。光谱测定表明MTX通过用柠檬酸分子的交换将MTX通过羧基（-COOH）的化学吸附到AgNP上。使用不同量的MTX合成的AgNP计算的药物加载能力为28,31和40％。体外药物释放试验描绘了所有缀合量的类似释放曲线，其释放在初始MTX的77-85％的初始MTX之间。关于游离MTX，添加纳米载波延迟其释放并改变了其药代动力学。在一阶动力学模型后3小时后，免费MTX释放，而在AgNPS存在下，在前5小时内观察到快速初始释放，然后在24小时后进行高原。在这种情况下，AgNPS-MTX安装了HIGUCHI模型，其中其溶解由扩散过程控制。由AgNPS-MTX处理的​​不同细胞系的流式细胞术中获得的结果证明了两种试剂的组合抗癌效果，在48小时暴露后降低结肠癌细胞系（HTC-116）中的活细胞的百分比下降至40％。这种效果较弱但肺癌细胞系（A-549）仍然很重要。最后，具有AgNPS-MTX的斑马鱼测定没有显示出任何显着的细胞毒性效应，从而通过偶联MTX来降低通过偶联至agnps实现的系统性药物毒性。这种观察到的斑马鱼模型的毒性降低也意味着AgNPS-MTX在对抗人类癌症中的使用可能性。

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  • 来源
    《RSC Advances》 |2020年第18期|共15页
  • 作者

    Rozalen M.; Sanchez-Polo M.; Fernandez-Perales M.; Widmann T. J.; Rivera-Utrilla J.;

  • 作者单位

    Univ Granada Fac Sci Dept Inorgan Chem E-18071 Granada Spain;

    Univ Granada Fac Sci Dept Inorgan Chem E-18071 Granada Spain;

    Univ Granada Fac Sci Dept Inorgan Chem E-18071 Granada Spain;

    Univ Granada Ctr Genom &

    Oncol GENYO Dept Genom Med Pfizer Avda Ilustrac 114 Granada 18016 Spain;

    Univ Granada Fac Sci Dept Inorgan Chem E-18071 Granada Spain;

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